Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.1.1.37 (
DNA methyltransferase
)
4,983
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Multiple regions on the chromosome arm 3p are frequently affected by loss of heterozygosity in human cancers. A candidate tumor suppressor gene is
TMEM7
, at 3p21.3, which encodes a transmembrane protein.
TMEM7
is expressed specifically in the liver, and the encoded protein shares substantial sequence homology with human and mouse 28-kDa interferon-alpha (IFN-alpha) responsive protein. In investigation of the possible role of
TMEM7
in development of hepatocellular carcinoma (HCC), we examined
TMEM7
expression in 20 primary HCC and 18 HCC cell lines and found recurrent functional alterations. Although
TMEM7
mRNA was expressed in normal hepatic cells, downregulation or inactivation of the gene was detected in 85% of primary HCC and 33% of HCC cell lines. To identify the mechanisms responsible, we examined genomic deletion and mutation, and also the effect of inhibitors of
DNA methyltransferase
and histone deacetylase on cells with low or no endogenous
TMEM7
expression. Homozygous deletion of
TMEM7
was not detected in 17 pairs of human HCC and corresponding noncancerous liver tissues, nor in any of the 18 HCC cell lines.
TMEM7
mutation was not detected in the 18 HCC cell lines (low or normal
TMEM7
expression). Treatment of two of six cell lines exhibiting downregulation or loss of
TMEM7
with 5-aza-2'-deoxycytidine and trichostatin A yielded additive increase in
TMEM7
expression, implicating aberrant DNA methylation and histone deacetylation in transcriptional silencing of this gene. Ectopic expression of
TMEM7
in two
TMEM7
-deficient HCC lines suppressed cell proliferation, colony formation, and cell migration in vitro and reduced tumor formation in nude mice. Treatment of two highly invasive HCC cell lines with IFN-alpha for 7 days significantly increased
TMEM7
expression and inhibited cell migration. These findings implicate loss of
TMEM7
expression in hepatocarcinogenesis and suggest that modification of
TMEM7
expression by IFN-alpha may have therapeutic relevance in a subset of HCC.
...
PMID:The interferon-alpha responsive gene TMEM7 suppresses cell proliferation and is downregulated in human hepatocellular carcinoma. 1769 85
